Faculty, Staff and Student Publications

Publication Date

2-20-2025

Journal

The Journal of Infectious Diseases

Abstract

Enterococci have evolved resistance mechanisms to protect their cell envelopes against bacteriocins and host cationic antimicrobial peptides (CAMPs) produced in the gastrointestinal environment. Activation of the membrane stress response has also been tied to resistance to the lipopeptide antibiotic daptomycin. However, the actual effectors mediating resistance have not been elucidated. Here, we show that the MadRS (formerly YxdJK) membrane antimicrobial peptide defense system controls a network of genes, including a previously uncharacterized 3-gene operon (madEFG) that protects the Enterococcus faecalis cell envelope from antimicrobial peptides. Constitutive activation of the system confers protection against CAMPs and daptomycin in the absence of a functional LiaFSR system and leads to persistence of cardiac microlesions in vivo. Moreover, changes in the lipid cell membrane environment alter CAMP susceptibility and expression of the MadRS system. Thus, we provide a framework supporting a multilayered envelope defense mechanism for resistance and survival coupled to virulence.

Keywords

Enterococcus faecalis, Anti-Bacterial Agents, Signal Transduction, Antimicrobial Peptides, Membrane Lipids, Cell Membrane, Drug Resistance, Bacterial, Antimicrobial Cationic Peptides, Animals, Bacterial Proteins, Gene Expression Regulation, Bacterial, Daptomycin, Stress, Physiological, Mice, Gram-Positive Bacterial Infections, Enterococcus faecalis, daptomycin, antimicrobial peptides, membrane lipids, cell envelope stress response

DOI

10.1093/infdis/jiae173

PMID

38578967

PMCID

PMC11841629

PubMedCentral® Posted Date

4-5-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

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